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Assessment of nanoindentation in stiffness measurement of soft biomaterials: kidney, liver, spleen and uterus.

ABSTRACT: Nanoindentation technology with high spatial resolution and force sensitivity is widely used to measure the mechanical properties of hard biomaterials and tissues. However, its reliability to analyze soft biomaterials and organs has not been tested. Here, we evaluated the utility of nanoindentation to measure the passive mechanical properties of soft biological specimen. Kidney, liver, spleen and uterus samples were harvested from C57BL/6 N mice. We assessed test-retest repeatability in biological specimen and hydrogel controls using Bland-Altman diagrams, intraclass correlation coefficients (ICCs) and the within-subject coefficients of variation (COVs). The results were calculated using Hertzian, JKR and Oliver & Pharr models. Similar to hydrogels, Bland-Altman plots of all biological specimen showed good reliability in stiffness test and retest examinations. In gels, ICCs were larger than 0.8 and COVs were smaller than 15% in all three models. In kidney, liver, spleen and uterus, ICCs were consistently larger than 0.8 only in the Hertzian model but not in the JKR and Oliver & Pharr models. Similarly, COVs were consistently smaller than 15% in kidney, liver, spleen and uterus only in the Hertzian model but not in the other models. We conclude that nanoindentation technology is feasible in detecting the stiffness of kidney, liver, spleen and uterus. The Hertzian model is the preferred method to provide reliable results on ex vivo organ stiffness of the biological specimen under study.

SUBMITTER: Wu G

PROVIDER: S-EPMC7606463 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background & aimsBoth liver stiffness (LS) and spleen stiffness (SS) are widely used to non-invasively assess liver fibrosis and portal hypertension, respectively. We aimed to identify the impact of disease etiology, namely the localization of inflammation (portal vs. lobular), on the SS/LS ratio.MethodsIn this multicenter study, LS and SS were prospectively assessed in 411 patients with alcohol-related liver disease (ALD) or hepatitis C virus (HCV) using FibroScan® (Echosens, Paris); changes in these parameters were also studied in response to treatment (alcohol withdrawal, HCV therapy). LS and spleen length (SL) were further analyzed in a retrospective cohort of 449 patients with long-term data on decompensation/death.ResultsBoth, SS and SL were significantly higher in HCV compared to ALD (42.0 vs. 32.6 kPa, p≪0.0001, 15.6 vs. 11.9 cm, p≪0.0001) despite a lower mean LS in HCV. Consequently, the SS to LS ratio and the SL to LS ratio were significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, p≪0.0001) through all fibrosis stages. Notably, SL linearly increased with SS and the relation between SS and SL was identical in HCV and ALD. In contrast, livers were much larger in ALD at comparable LS. After treatment, LS significantly decreased in both diseases without significant changes to the SS/LS ratio. In the prognostic cohort, patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%); liver failure was the major cause of death (p≪0.01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (p≪0.001).ConclusionBoth SS/LS and SL/LS ratios are significantly higher in patients with portal HCV compared to lobular ALD. Thus, combined LS and SS or SL measurements provide additional information about disease etiology and disease-specific complications.Lay summaryHerein, we show that patients with hepatitis C virus infection (HCV) have higher spleen stiffness and portal pressure than patients with alcohol-related liver disease (ALD), within the same fibrosis stage and matched to liver stiffness. Thus, the spleen stiffness to liver stiffness ratio is significantly higher in patients with HCV compared to ALD. Additionally, patients with HCV more commonly progress to portal hypertension-related complications (e.g. variceal bleeding), while patients with ALD more commonly progress to liver failure (e.g. jaundice). The spleen stiffness to liver stiffness ratio is a useful tool to confirm disease etiology and predict disease-specific complications.

Project description:BackgroundThe value of magnetic resonance elastography (MRE) in portal hypertension (PH) has yet to be determined in the context of chronic liver disease (CLD). This study examined the value of MRE for the prediction of hepatic venous pressure gradient (HVPG) and high-risk esophageal varices (EVs) in a CLD cohort with a generally high HVPG.MethodsPatients with CLD who underwent both HVPG measurement and two-dimensional MRE examination at Beijing Friendship Hospital between April 2018 and March 2022 were prospectively included. Two-dimensional MRE was performed within the liver and spleen. Endoscopy results and laboratory parameters were collected. Some selected published serum markers were calculated, including fibrosis 4, aspartate aminotransferase-to-platelet ratio index, and King's score. The efficacy of the parameters for assessing PH was analyzed by using the Pearson correlation coefficient, linear and logistic regression, and receiver operating characteristic curve analyses.ResultsA total of 48 patients were included. The mean HVPG was 16.8±5.8 mmHg. Among these patients, 47 patients had PH (HVPG >5 mmHg), and 43 patients had clinically significant PH (HVPG ≥10 mmHg). Among the parameters associated with HVPG, the strongest correlation was found for spleen stiffness (SS) (R=0.638; P<0.001). In multiple regression analyses, SS was independently associated with an elevated HVPG and high-risk EVs. The areas under the receiver operating characteristic curve of SS for identifying patients with an HVPG ≥16 mmHg, HVPG ≥20 mmHg, and high-risk EVs were 0.790, 0.822, and 0.886, respectively, which were higher than those of liver stiffness (LS) and serum markers but slightly inferior to that of fibrosis 4 (area under the receiver operating characteristic curve =0.844) in identifying an HVPG ≥16 mmHg. SS cutoff values of 9.5, 10.05, and 9.9 kPa were selected to rule out the presence of an HVPG ≥16 mmHg, HVPG ≥20 mmHg, and high-risk EVs (sensitivity: 100%, 100%, and 100%, respectively; specificity: 45.5%, 50%, and 60%, respectively).ConclusionsIn patients with generally high HVPG, SS measured by two-dimensional MRE may be a better predictor of HVPG values and high-risk EVs than LS and serum markers.

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Assessment of nanoindentation in stiffness measurement of soft biomaterials: kidney, liver, spleen and uterus.

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